Bernard Corenblum

Hyperinsulinemia in polycystic ovary syndrome correlates with increased cardiovascular risk independent of obesity

OBJECTIVE To assess the role of insulin resistance, independent of obesity, in determining cardiovascular risk among women with the polycystic ovarian syndrome (PCOS). DESIGN Cross-sectional study examining the relationships between hyperinsulinemia, composite cardiovascular risk scores, and prevalence of individual risk factors among lean and obese women with PCOS and healthy controls. SETTING University-based tertiary care outpatient endocrinology clinic. PATIENT(S) 57 women with clinically defined PCOS and 45 unselected healthy age-matched controls. INTERVENTION(S) Clinical and anthropomorphic measurements and laboratory determinations of insulin and lipid levels. MAIN OUTCOME MEASURE(S) Fasting serum insulin and a cardiovascular risk score. RESULTS Hyperinsulinemic women with PCOS carried more cardiovascular risk than their normoinsulinemic counterparts, who in turn had more risk than the control women (P=.004 by analysis of covariance). In addition to the lipid changes expected with insulin resistance (high triglyceride and low HDL cholesterol levels), there was an excess of LDL cholesterol among the women with PCOS (P=.006 by analysis of covariance). Across the range of body mass index, women with PCOS had greater insulin resistance than controls, suggesting that PCOS itself and body mass index both contribute to the observed insulin resistance. CONCLUSIONS Our data support the hypothesis that insulin resistance in PCOS is a determinant of overall cardiovascular risk independent of obesity. The mechanism of this relationship remains uncertain and is the subject of ongoing research.

The safety of physiological estrogen plus progestin replacement therapy and with oral contraceptive therapy in women with pathological hyperprolactinemia

In summary, E- replacement therapy may be administered to women with E deficiency, despite the presence of pathological hyperprolactinemia, with apparently no adverse effect on the underlying disease process. The concern of induction of rapid growth of an underlying pituitary adenoma was not substantiated.

The hyperprolactinemic polycystic ovary syndrome may not be a distinct entity

Thirteen women with hyperprolactinemia and clinical stigmata of the polycystic ovary syndrome (PCO) had their serum prolactin (PRL) response to thyrotropin-releasing hormon (TRH) compared with two other groups of PCO. One PCO group had an elevated ratio of basal luteinizing hormone (LH) to follicle-stimulating hormone (FSH), and another had a normal ratio of basal LH to FSH. The PRL response to TRH was similar in hyperprolactinemic PCO and elevated LH PCO, and both were significantly greater than normal LH PCO and normal women. This suggests the hyperprolactinemic polycystic ovary (HPCO) is probably produced by similar central and/or peripheral mechanisms that result in the production of an elevated serum LH. These two features are probably associated in a common pathophysiologic mechanism. The HPCO syndrome does not appear to be a distinct entity but clinically must be differentiated from other causes of mild hyperprolactinemia.

The effect of a progestin on gallbladder function in young women

Female sex hormones have been considered to be a risk factor for the development of cholesterol gallstone disease, because of increased cholesterol saturation of bile. Impaired gallbladder function is an additional factor which is suspect but unproved. We investigated gallbladder function in 10 young women on two occasions: first during the follicular phase of the menstrual cycle, when endogenous progesterone is low, and again after the ingestion of medroxyprogesterone acetate, 10 mg/day for 10 days, just prior to the next menstrual period. Another group, 15 young women, was studied during their luteal phase, when endogenous progesterone is high. Gallbladder filling and emptying in response to cholecystokinin (0.02 U/kg-min) was quantitated by 99mTc-HIDA cholescintigraphy. Gallbladder filling and emptying were no different in women in the follicular phase than in women in the luteal phase of the menstrual cycle. In both menstrual phases, the administration of the exogenous progestin significantly (p less than 0.05) reduced the fraction of hepatic bile entering the gallbladder. Gallbladder emptying was also depressed: the total amount ejected was less, the time to empty half the contents was prolonged, and the rate was slower (p less than 0.05). Thus, different phases of the normal menstrual cycle do not appear to have any effect on gallbladder function. Administration of an exogenous progestin, however, significantly impairs both gallbladder filling and emptying, factors which could predispose to the formation of cholesterol gallstones.

Long-term follow-up of hyperprolactinemic women treated with bromocriptine.

Seventy-five women with hyperprolactinemia and demonstrable or suspected prolactinomas were treated with bromocriptine only and followed for 5 to 9 years. Biochemical, radiologic, and clinical responses were generally maintained in the long term, once established in the short term. Underlying mass effects on neurologic and pituitary function tended to improve, and no tumor progression was noted. Hypogonadal symptoms normalized in 68 of 75 women. Bromocriptine responses in long-term follow-up do not demonstrate any cumulative problems not seen in short-term therapy.

Mechanisms of Control of Prolactin Release in Response to Apprehension Stress and Anesthesia-Surgery Stress *

The response of prolactin to stress may not be controlled by a single mechanism. This study was designed to measure the prolactin response in the human female to two reproducible stresses: the apprehension (A) prior to surgery (laparoscopy and hysteroscopy) and the stress of the anesthesia-surgery (AS). Attempts to modify the release of prolactin was made by pharmacologic means. Thirty-eight normally menstruating women served either as controls or received histamine (H1), serotonin, opioid, or dopamine receptor-blocking agents and the prolactin response was measured. The release of prolactin to AS was blunted by higher-dose of opioid and by dopamine antagonists. The A release of prolactin was enhanced by the dopaminergic antagonist and blunted by the other three agents. It was concluded that the mechanism for the stress-induced release of prolactin may vary depending upon the nature of the stress.

Successful Outcome of Ergocryptine-Induced Pregnancies in Twenty-One Women with Prolactin-Secreting Pituitary Adenomas

The natural history of prolactin-secreting adenomas is not known. For this reason, optimal therapy for women harboring these adenomas who desire to conceive is also unknown. Argument can be found to favor surgical excision, radiation therapy, prolactin-suppressing chemotherapy, and clinical observation. In a large series of women with prolactin-secreting pituitary adenomas, 21 have conceived and delivered healthy infants, all of whom had ergocryptine-induced prolactin suppression as the sole form of therapy. Endocrinologic, neurologic, biochemical, and radiologic assessment failed to demonstrate any obvious growth of the pituitary adenoma, except for slight enlargement of the sella turcica in one patient who delivered twins. The failure to demonstrate any worsening of the clinical state may reflect the fact that no large tumors were included in this series, only small but definite microadenomas found on sellar tomography. All of the various modalities of therapy must be considered with each patient, but this series suggests that ergocryptine treatment with careful clinical follow-up is relatively safe in patients with small pituitary tumors.

Bromocriptine Reduction of Prolactinoma Size

Eight consecutive patients with large prolactinomas, as assessed by elevated serum prolactin concentrations and suprasellar extension of the visualized pituitary adenoma on computerized tomographic (CT) scanning, were treated with bromocriptine. With prospective evaluation all eight patients demonstrated disappearance of symptoms ascribed to both the hyperprolactinemia and the tumor itself, and all eight showed a decrease in tumor size within 3 months, as assessed by CT scanning. This prospective study demonstrates that the reduction in size of a large prolactinoma by bromocriptine is commonly observed and should be considered as an initial form of therapy for such patients.

A Rationale for the Use of Bromocriptine in Patients with Amenorrhea and Normoprolactinemia

The return of menses in amenorrheic normoprolactinemic women after treatment with bromocriptine is well documented. To determine whether an increased pituitary prolactin-secreting capacity may be the underlying mechanism, 14 women with amenorrhea were studied. None complained of galactorrhea, but in all 14 it was possible to express a few drops of milk from the nipple. All women were normoprolactinemic and had normal sellar tomography. A standard thyrotropin-releasing hormone (TRH) test was performed and bromocriptine (2.5 mg twice daily) was administered. Within 8 weeks, 9 of 14 patients had return of menses. The second group of five patients did not respond to bromocriptine. The mean prolactin response to TRH was significantly greater in those women who experienced return of menses, although there was individual overlap between both groups. This finding suggests that enhanced prolactin secretory capacity may account for amenorrhea is some apparently normoprolactinemic patients. The TRH test may serve to identify those patients who may benefit from bromocriptine.

Subtle abnormalities in follicular development and hormonal profile in women with unexplained infertility.

A prospective study of six unselected couples diagnosed as having unexplained infertility was done. In three of six patients, subtle abnormalities in follicular development were detected. In the first case poor follicular growth was observed. There was a premature small rise of luteinizing hormone (LH) with subsequent low levels of estradiol (E2) in the late follicular phase and unusual wide LH peak. This was followed by low progesterone levels in the luteal phase. In the second case follicular growth was abrupted by premature LH surge. This surge was triggered by early rise of E2 level while the follicle was still small in size. In the third case luteinized unruptured follicle syndrome was diagnosed, on ultrasound examination. All of the abnormalities were repetitive.